AB0878 SAFETY AND EFFICACY OF MESENCHYMAL STEM CELLS TRANSPLANTATION IN SYSTEMIC SCLEROSIS
Authors: N. Krivoruchko, L. Zaripova, M. Askarov, A. Baigenzhin, T. Karibekov, G. Shaimardanova, S. Bekturganova
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic sclerosis (SSc) is a systemic autoimmune disease characterised by vasculopathy and tissue fibrosis of the skin and various internal organs. Currently available treatments for SSc have limited efficacy, and the disease still has poor prognosis. New therapeutic approaches such as mesenchymal stem cell (MSC) transplantation are of great interest. MSCs are known as multi-potent progenitor stromal cells that self-renew and differentiate toward multiple mesenchymal cell lineages [1, 2]. <h3>Objectives</h3> to evaluate the efficacy and safety of bone marrow MSCs transplantation in SSc. <h3>Methods</h3> Twenty-five patients with a reliable diagnosis of SSc refractory to classical immunosuppressive therapy were divided between main and control group. Patients from the main group underwent transplantation of MSCs in combination with high-dose immunosuppressive therapy (HIST) (n=14), while the control group was observed on the background of traditional immunosuppressive therapy without cell transplantation (n=11). Both groups were comparable in age, gender of patients, duration and severity of the disease. The degree of induration of the skin was evaluated using the modified Rodnan skin score (mRSS). The disease activity was assessed using the EScSG scale. Anti-nuclear antibodies (ANA), anti-SCL-70 were examined by indirect immunofluorescence, cytokines (IL-1Β, IL-6, IL-10, TNF-α) - by ELISA. All patients underwent CT scan of the thoracic segment, echocardiography with determination of mean pulmonary artery pressure (mPAP) and spirography. Statistical analysis was carried out by GraphPad Prism version 8. <h3>Results</h3> Before MSC transplantation, SSc patients in both groups demonstrated an increase in ANA, C-reactive protein (CRP), IL-1, IL-6, TNFα, with the background of severe skin induration. After transplantation of MSCs with HIST a pronounced clinical effect was noted: induration and dense swelling of skin, muscle contractures, vasospasm attacks (Raynaud syndrome) significantly decreased, dysphagia was relieved. In addition, a significant decline in skin density according to mRSS was observed (from 22.13±2, 52 to 9.8±0.93, p=0.03). A significant reduction in EScSG was registered from 3.21 to 2.48 points (p=0.05). Six months after transplantation patients with SSc demonstrated a decrease in CRP from 10.14±2.01 to 3.28±1.31. Parameters of the cytokine profile with a moderate decrease for IL-1, IL-6 and TNFα (p&lt;0.05). According to the results obtained patients who underwent BM-MSCs transplantation demonstrated 54% decrease in mPAP, from 41.4 ± 10.87 to 26.8 ± 3.27. In SSc patients in the control group high levels of cytokines, mRSS, and mPAP were recorded during the observation period. No cases of death or severe complications associated with MSCs transplantation with HIST have been registered. <h3>Conclusion</h3> The conducted research demonstrated the therapeutic effect of MSC transplantation consisted in the decrease of the induration of skin, the activity of SSc and the severity of pulmonary hypertension, as well as normalizing the levels of proinflammatory cytokines. <h3>References</h3> [1]Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-7. [2]Berebichez-Fridman R, Montero-Olvera PR. Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review. Sultan Qaboos University medical journal. 2018;18(3):e264-e77. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.